After weeks of vignettes airing, Duprée made his first appearance in WWE on the April 28, 2003 episode of Raw, alongside Sylvain Grenier as La Résistance, and attacking Scott Steiner. La Résistance went on to feud with Scott Steiner and Test, who was forced to be Steiner's tag team partner by Stacy Keibler. La Résistance ended up defeating Steiner and Test at Judgment Day on May 18, 2003 in the team's pay-per-view debut.
On June 15, 2003, La Résistance won the World Tag Team Championship from Kane and Rob Van Dam at Bad Blood.
The third member of La Résistance, Rob Conway, was originally introduced as an unnamed American serviceman being abused by Grenier and Duprée. When The Dudley Boyz came out to attack La Résistance, they brought Conway into the ring with an American flag. Once the Dudley Boyz had their backs turned, Conway attacked them with the American flag and then tore it off the pole and laid it on top of them. Conway, now renamed to Robért Conway, joined Duprée and Grenier and the trio began carrying the French flag to ringside and singing the French national anthem before their matches. La Résistance dropped the titles to the Dudley Boyz at Unforgiven in a three-on-two handicap tables match. The trio went on to feud with several tag teams, including the Dudley Boyz, Rosey and The Hurricane, and Garrison Cade and Mark Jindrak.
In October 2003, Grenier suffered a back injury. Duprée and Conway held the tag team together until Grenier returned in the Spring of 2004. At Armageddon, La Résistance competed in a tag team turmoil match for the World Tag Team Championship, which was won by Ric Flair and Batista. At the Royal Rumble, Duprée competed in the 30-man Royal Rumble match, where he eliminated Matt Hardy before getting eliminated by Rikishi. At WrestleMania XX, La Résistance (Duprée and Conway) competed in a fatal four-way tag team match for the World Tag Team Championship, but failed to win the titles. Grenier returned in March 2004, thus reuniting the trio. The reunion did not last long, as Duprée was the first pick in the 2004 WWE Draft Lottery on March 22.
Duprée made his SmackDown! debut on the March 25, 2004 episode of SmackDown!, defeating Billy Kidman. He briefly had a talk show on SmackDown!, called "Cafe de René", but his only guest was Torrie Wilson as the segment was cancelled after only one night. Duprée wrestled Wilson to a draw on the April 27, 2004 edition of SmackDown. For several months, he pursued the United States Championship, held by John Cena. After an incident that happened during his "Cafe de René" (the same incident involving Torrie Wilson), Duprée challenged Cena to a championship match. The match was granted by the then-SmackDown! general manager Kurt Angle and it took place at Judgment Day. Cena retained the championship when he pinned Dupree after executing an F-U. At The Great American Bash, Duprée competed in a four-way elimination match for the WWE United States Championship, which saw Cena retain once again.
After losing to Cena, he focused on the WWE Tag Team Championship and eventually won the titles with Kenzo Suzuki on September 9. At No Mercy, Duprée and Suzuki defeated Rob Van Dam and Rey Mysterio to retain the titles. They lost the championship on the December 9 episode of SmackDown! to Van Dam and Mysterio. This match happened just days before Van Dam and Mysterio were to challenge Duprée and Suzuki at Armageddon. At the pay-per-view, Duprée and Suzuki had a championship rematch, but they were unable to regain the tag title. At the 2005 Royal Rumble, Duprée competed in the 30-man Royal Rumble match, where he was eliminated by Chris Jericho. On the February 20 edition of Sunday Night Heat (before the No Way Out pay-per-view), Duprée and Suzuki faced Hardcore Holly and Charlie Haas in a losing effort.
On the March 24, 2005 airing of SmackDown!, he was "sacrificed" by The Undertaker as a message to Randy Orton (regarding their match at WrestleMania 21), when The Undertaker interrupted a match between Duprée and Booker T. The result of the "sacrifice" saw Duprée receiving a Tombstone Piledriver on the steel steps which lead up to the ring. Duprée was taken off television after this, working dark matches until the April 28 edition of SmackDown!, where he was defeated by John Cena. Duprée went back to dark matches and a few Velocity matches until the June 18 episode of Velocity, where Duprée came out calling himself "The French Phenom", defeating Mark Jindrak via submission. The following week on Velocity, Duprée came out with a new look, sporting black trunks with his initials as well as jet black hair and a Dalí-styled goatee.
On June 30, Duprée became one of the last minute trades in the 2005 WWE Draft Lottery, which saw him jump from SmackDown! back to Raw. On the July 4 edition of Raw, Duprée re-debuted with his French Phenom gimmick and defeated Val Venis on the same night. Duprée began cutting promos using a new quote referring to himself as "Simply Phenomenal". Duprée also began a winning streak against superstars such as The Hurricane, Matt Striker and Tajiri before suffering a near career-ending hernia in mid-September.
On the August 8, 2006 episode of ECW on Sci Fi, a promo aired with Duprée, sporting a clean shave and long hair, announcing that he would be debuting for the brand soon. Promos aired throughout the rest of August showing Duprée taking pictures, posing in mirrors, and working out, while claiming he is "the most extreme athlete in ECW history". Duprée made his ECW debut on September 12, 2006, defeating Balls Mahoney. On the February 20, 2007 episode of ECW on Sci Fi, Duprée reformed La Résistance with Sylvain Grenier, but the team's reunion was short-lived after Duprée was suspended at the start of March and sent to rehab after violating the Health and Wellness policy.
Duprée was released from his WWE contract on July 26, 2007.